Co-agonist therapeutics come of age for obesity

Glucagon-like peptide 1 (GLP1) analogues are licensed options for obesity, but new treatments are required to obtain better weight loss and to directly address other co-morbidities, such as non-alcoholic fatty liver disease. Research published in 2022 shows that co-agonist combinations of GLP1 with other hormones provide clinically important advances.

Key advances

• In the SURMOUNT-1 trial for obesity, adults with overweight or obesity without type 2 diabetes mellitus achieved placebo-subtracted weight loss of up to 20% after 72 weeks of the GLP1–GIP receptor co-agonist tirzepatide, with a similar safety profile to high-dose semaglutide⁵.

• Findings published in a preprint from a phase I clinical trial on the GLP1–glucagon receptor co-agonist NN1177 in adults with overweight or obesity have raised problems with deterioration of glucose tolerance and other safety concerns, despite inducing weight loss, which illustrates the difficulties in getting the agonist balance right during the preclinical development of co-agonist therapies^6,7.

• Preclinical and phase I clinical trial data for a triple GLP1–GIP–glucagon receptor co-agonist therapy (LY3437943) suggest that it is effective at inducing weight loss, without inducing adverse effects that would require discontinuation; adverse effects were gastrointestinal in nature, similar to GLP1 receptor agonists⁹.